This project will develop a tunable theranostic probe that can support the diagnosis, therapy and therapy guidance in one process in individual specific cells. This will be realized by developing a plasmonic nanobubble (PNB), which is not a particle but an event (transient vapor nanobubble) that is generated on-demand with a short laser pulse around gold nanoparticles targeted to specific cells. Basic biomedical properties of the PNB are related to their optical scattering and mechanical impact and are determined by the PNB diameter that can be tuned starting from 50 nm by varying the energy of the excitation laser pulse. By tuning the size and lifetime of the intracellular PNB, we will realize high-sensitive imaging, controllable delivery, selective cell damage, and optical guidance of the above processes. We will achieve several specific biomedical functions of the PNB: imaging with significantly (100-fold and higher) improved sensitivity and contrast, delivery of molecular loads through controllable localized disrupting of the membrane (of the liposome, of the cell or of the endosome), and cell mechanical (non-thermal) damage with larger PNBs. After determining the mechanisms of biological effects of the PNB, we will combine its different functions into one fast sequence to provide diagnosis, treatment and treatment guidance at the individual cell level. This will be achieved by real-time tuning of the PNB function with several laser pulses and will deliver a cell theranostic process of less than one microsecond duration. Being a stealth, on-demand probe with tunable function, the PNB can be applied to all areas of medicine since the PNB mechanism is universal and can also be employed for detecting and manipulating specific molecules, or for precise microsurgery. PUBLIC HEALTH RELEVANCE: This project is aimed at the development of tunable devices (nanoprobes) called plasmonic nanobubbles that can carry out biomedical diagnosis and therapy in a single fast process at cell level. Such transient bubbles are generated around gold nanoparticles with a short single laser pulse. By tuning dynamically their size we will tune their biological action from a non-invasive sensing, to localized intracellular drug delivery, and to selective elimination of specific cells. Due to their unique tunability of optical and mechanical properties, plasmonic nanobubbles will impact wide areas of research, diagnosis, therapy and micro-surgery by providing the novel universal and efficient nanoprobe.